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Mechanisms of vaccine interference induced by pre-existing anti-staphylococcal antibodies and B cells

Award Number: R01AI190409
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/20/2026
PERIOD OF PERFORMANCE END DATE: 02/21/2026

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Mechanisms of vaccine interference induced by pre-existing anti-staphylococcal antibodies and B cells - Abstract / Summary Staphylococcus aureus (SA) navigates a dual role as both a symbiont and an occasional deadly pathogen, yet no successful vaccines exist to combat SA infection in human. Although exposure to SA in both human and mouse generates robust anti-SA antibodies (anti-SA Ab), these antibodies only provide modest or no signification protection against SA infection. Recently, we identified a likely reason behind the failure of clinical SA vaccines. Our research demonstrates that SA-exposed mice develop anti-SA Ab with shifted epitopes and increased Fc sialylation, which are ineffective in supporting the killing of pathogen both in vitro and in vivo. Staphylococcal vaccination of SA-exposed mice recalls this non-protective immune imprint, thereby interfering with vaccine efficacy. To understand the mechanism behind this vaccine interference, we show that SA-induced inflammatory cytokines directly upregulate sialyltransferase expression, enhancing Fc sialylation and undermine Fc function. Interestingly, the administration of pre-existing anti-SA Ab during staphylococcal vaccination compromises the vaccine efficacy. Furthermore, we show that SA-induced IL-10-secreting suppressive B cells interfere with vaccine responses. Based on these findings, we hypothesize that SA-induced IL-10 disrupts the germinal center reaction, leading to the development of suppressive B cells and non-protective anti-SA Ab thereby interfering with vaccine responses. To test our hypothesis, 1) we propose to study SA- and adjuvant-induced pro- and anti-inflammatory cytokines and their link to humoral vaccine efficacy through distinct antibody glycosylation; 2) we will investigate how SA-B cells limit the germinal center reaction and identify intracellular signaling pathways that control the development of suppressive B cells; 3) finally, we will address the mechanism of pre-existing anti-SA Ab in antigen clearance, epitope masking and shifting in SA infection and SA vaccine, and assess the impact of maternal-derived anti-SA antibodies in neonatal SA vaccination. Overall, our proposal aims to understand the interaction between SA and adjuvant-induced inflammatory cytokines, host humoral immunity, and vaccine to provide new insights for developing effective vaccine approaches in neonate.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $804,705 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	2/20/2026	NEW	$804,705
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	003	1	7/6/2026	NEW	$0
2026	2026	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	002	2	6/30/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$799,380
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	1	6/30/2026	NEW	-$799,380
														Subtotal = $804,705

Grand Total All Awards = $804,705

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Mechanisms of vaccine interference induced by pre-existing anti-staphylococcal antibodies and B cells

Award Number: R01AI190409

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/20/2026

PERIOD OF PERFORMANCE END DATE: 02/21/2026

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